1. Field of Invention
The present invention relates generally to a method and apparatus to form sterile connections, and more particularly, a method and apparatus for inexpensively creating sterile connections in non-sterile environments.
2. Background of the Invention
Presently, the pharmaceutical industry is comprised of two manufacturing systems. The first manufacturing system is the traditional system that uses clean rooms, stainless steel reactors, holding tanks, and piping to maintain sterile conditions during manufacture. The second manufacturing system is state-of-the-art biotechnology manufacturing that uses an assortment of disposable plastic bags and flexible sterile tubing. With the traditional manufacturing methods, clean-in-place and steam-in-place systems are required to assure that the stainless steel reactors and piping remain clean and sterile. A sterile clean room is also required during traditional manufacturing processes so that when necessary connections are made that breach the sterile piping, the environment does not contaminate the fluid flow. Maintaining a clean room is time consuming and difficult to validate. In contrast, the state-of-the-art biotechnology methods use plastic bags and tubing sets that can be sterilized prior to implementation in the manufacturing process and are completely disposable. Biotechnology manufacturing methods require significantly less capital because no initial investment in expensive stainless steel reactors or piping is required.
The tubing in biotechnology manufacturing is used between process containers and equipment that require sterile connections. A sterile tube welding machine can be used to weld the thermoplastic tubing in a sterile manner without the need for a laminar flow cabinet or similar environmental control device. The tube welder sterilizes a cutting blade or wafer then moves the blade through the two ends of the tubing to be joined. Once both ends of the tubing have been cut, the machine aligns the ends of the tubes while maintaining a high temperature. After the thermoplastic tubes cool, a sterile weld is formed. Another system utilizes a self contained HEPA system and a sterile plastic connector to create the union; still using the heated blades.
The various types of sterile tubing welders have disadvantages in that there is a limited range of the size of tubing that can be welded by one particular tube welding machine. A tube welding machine is also usually limited in applicability to specific tube materials such as thermoplastic. Furthermore, tube welding machines are typically large, heavy, lack versatility, and expensive.
The biotechnology approach, out of necessity, requires large amounts of disposable flexible tubing. This tubing is used to convey the sterile contents of one bag to another. Each time a connection is made to add or remove contents of a bag, only one of four systems noted below can be used; each system has significant shortcomings.
All of the systems listed above require the use of thermoplastic tubing (no silicone) except the manual system. The ideal aseptic/sterile connection system would have the following characteristics:
1. Applicability to a wide array of tubing materials and sizes;
2. Inexpensive to assemble and maintain;
3. Requires no capital equipment;
4. Operates without a clean room;
5. Disposable;
6. Reliable and repeatable; and
7. Operator independent.
The current systems in use presently fall short of meeting the ideal criteria. Thus, there is a need for a disposable aseptic connection system that does not require a tube welding machine. A disposable aseptic connection system that does not employ a tube welding machine could be used regardless of the tubing material, size or location, at a competitive cost. Additionally, once a company commits to this type of connector, all pre-sterile bags and tube sets can be supplied with the appropriate disposable aseptic connection system fittings already in place. Therefore, connections are simple, repeatable and validatable.
Prior art describes varying apparatus for accomplishing sterile connections using a disposable aespetic connection system. By way of example, U.S. Pat. No. 4,418,945 to Kellog describes sterile connectors having strips that are withdrawn to expose the ends of conduits attached to cooperating connectors. U.S. Pat. No. 4,149,534 to Tenczar describes sterile connectors for joining conduits having an adhesive release positioned on adjoining faces of the connectors. U.S. Pat. No. 4,030,494 to Tenczar describes sterile fluid connectors having cooperating heat penetratable and fusible plastic barriers for coupling two conduits. U.S. Pat. No. 4,022,205 to Tenczar describes sterile fluid connectors having cooperating adhesive surfaces that are jointly punctured upon coupling two conduits. U.S. Pat. No. 4,019,512 to Tenczar describes an adhesively sterile connector having a protective member that is progressively pulled away. U.S. Pat. No. 3,865,411 to Rowe et al. describes a sterile connector having an adhesive release and two connectors are used to make a connection. Rowe et al. teaches to align the adhesive portions; then the free ends of the adhesive are pulled thereby exposing the free ends of the connectors to form a sealed, sterile fluid passage.
Notwithstanding the existence of such prior art disposable aseptic connection systems, there is a need for an improved and more efficient apparatus and method for using a disposable aseptic connection system that can be used as either a temporary or permanent connection.
An objective of the present invention is to provide a disposable aseptic connection system that is a temporary and disposable connection.
Another objective of the present invention is to provide a disposable aseptic connection system that is adaptable to a permanent connection.
Another objective is to provide a connection that is reliable and repeatable.
Still another objective is to provide a disposable aseptic connection system that is operator independent.
Another objective is to provide a connection system that is applicable to a wide array of tubing materials and sizes.
Another objective is to provide a disposable aseptic connection system that is inexpensive to assemble and maintain and requires no expensive equipment.
Another objective is to provide an aseptic connection system that can operate without a clean room.
Another objective is to provide a connection means that is compatable with the standard sanitary fittings common to the biotechnology industry.
It is, therefore, to the effective resolution of the aforementioned problems and shortcomings of the prior art that the present invention is directed.
However, in view of the prior art at the time the present invention was made, it was not obvious to those of ordinary skill in the pertinent art how the identified needs could be fulfilled.
The present invention solves significant problems in the art by providing an apparatus for establishing an aseptic/sterile connection comprising a substantially flexible, substantially transparent sterile barrier enclosing a terminal end of a conduit, a resilient, deformable support card fixed to the sterile barrier having an outer face disposed about the terminal end of the conduit having an adhesive perimeter covered by a release paper, and a rolling membrane comprising a continuous, removable, yieldable, flexible strip material, a portion of which is removably adhered to the support card and overlies the end of the conduit, the rolling membrane having a free end whereby a force applied to the free end thereof withdraws the entire rolling membrane to expose the end of the conduit whereby an aseptic/sterile connection is achieved by adhering opposing support cards together, removing the rolling membrane thereby creating a sterile corridor between a first sterile barrier and a second sterile barrier, and mating the terminal end of a first conduit and a second conduit together.
Adhesive material is applied to the exposed side of the rolling membrane while the side of the rolling membrane abutting the sterile barrier enclosure is free of adhesive material and treated with a release coating. This is preferred so that no residue of adhesive could possibly contaminate a fluid path established through the sterile corridor.
A biocidal agent may be integrated into the adhesive perimeter and the rolling membrane to combat contamination by both fungi and bacteria. A variety of biocides may be utilized such as Intercide(copyright) ABF available from Akros Chemicals America in New Brunsick, N.J.
An important aspect of the invention is that each opposing connection is oriented in the proper fashion. The rolling membrane on each opposing connection must be correctly oriented or the membrane will be impossible to properly withdraw. If the opposing support cards are adhered in an incorrect orientation, a sterile connection cannot be made and the support cards must be pulled apart and discarded. To prevent incorrect orientation of the support cards, an embodiment of the present invention includes an orientation-specific latching means on the support card wherein two opposing support cards may only latch together in a single orientation. This is achieved by configuring each latch point in a predefined, geometric configuration. The orientation-specific latching means mechanically biases two opposing support cards together to provide a sterile connection.
In one embodiment of the invention, the novel connector is used with annular sanitary fittings. One and one half inch diameter sanitary fittings are standard in the biopharmaceutical manufacturing art. Polymer snap fittings are mechanical latches including one or more latching arms and corresponding latching notches. The latches in this embodiment snap together in an internal circumferential direction to form a genderless connector. The genderless connector provides the advantages of easy manipulation and reduced inventory requirements.
An internal circumferential direction defines a direction of the latches that snap together around the circumference of the inside of opposedly aligned fittings. The circumferential latches provide the proper orientation of one fitting relative to the other to ensure that the opposedly aligned rolling membranes achieve a sterile connection. Snap fittings are not capable of maintaining a sterile connection indefinitely due to the creep characteristics of the polymer. Therefore, a polymer snap fitting requires additional support to provide a permanent sterile connection. Prior art snap fittings include externally located latches so that the standard sanitary clamps cannot be used. However, the present embodiment of the novel invention provides low profile latches with internal circumferential orientation so that standard stainless steel clamps can be used in adapting the snap fitting connection to a permanent connection. Stainless steel sanitary clamps are readily available in the industry and can be used to adapt the novel temporary snap fitting connection to a permanent connection at the operatorxe2x80x3s discretion. The stainless steel clamp encircles and permanently secures the snap fitting.
The properly aligned and opposedly aligned support cards that are coupled with the mechanical latching means results in the joining of both rolling membranes whereby adhesion of the rolling membranes is constrained to be simultaneous. Therefore, the sterile surface of one card to that of the opposing card is exposed concurrently forming a sterile connection.
The invention further comprises a resilient gasket surrounding the periphery of the terminal end of the conduit wherein opposing gaskets are mechanically biased against each other thereby forming a substantially fluid-tight connection between two conduits.
An advantage of the current invention is that the connection can be used as a temporary connection or adapted to a permanent connection with the use of a standard stainless steel clamp. Thus, two markets are served.
Another advantage of the present invention is the internal circumferential latching means that orientates one fitting to the other to assure alignment of one rolling membrane with the other. A radially directed latch would require a longer latch length and would then interfere with the clamp or require design modifications to the tapered section of the fitting around which the clamp rests. However, the present invention has the advantage that it can be used with standard sanitary fittings and the novel latching means can be manually activated or will be automatically engaged when the clamp is closed.
These and other important objects, advantages, and features of the invention will become clear as this description proceeds.
The invention accordingly comprises the features of construction, combination of elements, and arrangement of parts that will be exemplified in the description set forth hereinafter and the scope of the invention will be indicated in the claims.